Central administration of obestatin fails to show inhibitory effects on food and water intake in mice

Obestatin is a ghrelin-associated peptide hormone with presumed anorexigenic and inhibitory effect on gastric propulsive motility activity. Recent literature, however, discloses much contestation over satiety and gastrointestinal motility-related functionalities of obestatin. In addition, antidipsinogenic effects in rodents by obestatin were recently reported. The present study was set up to bring more clarity into the contested effects of obestatin on food and water intake. Additionally, the stability of obestatin in brain tissue homogenate was investigated. The in vitro incubation of obestatin in brain homogenates revealed disappearance half-life times of 19 min for crude brain homogenate to 27 min for brain membrane homogenate. For the behavioural studies, male C57Bl/6 mice were intracerebroventricularly treated with 0.2 nmol murine amidated obestatin or vehicle at the age of 3 months. An additional group of mice was treated with 0.3 nmol of corticotropin releasing factor (CRF) as a positive control of suppression of food intake. Food and water intake were studied over a period of 5 h in metabolic cages. Under our experimental conditions, no suppressive effects of obestatin on food or water intake were observed, whereas CRF evoked a significant suppression of food intake, which proves the internal validity of the study design.